Normally, 7-8% of human body weight
is from blood. In adults, this amounts to 4.5-6 quarts of blood.
This essential fluid carries out the critical functions of transporting
oxygen and nutrients to our cells and getting rid of carbon dioxide,
ammonia, and other waste products. In addition, it plays a vital role
in our immune system and in maintaining a relatively constant body
temperature. Blood is a highly specialized tissue composed of more
than 4,000 different
kinds of components. Four of the most important ones are red cells,
white cells, platelets,
and plasma. All humans produce these blood
components--there are no populational or regional differences.

Red
Cells

Human
erythrocytes or "red cells"
(cell diameter about .0003 inches)

Red cells, or erythrocytes, are
relatively large microscopic cells without nuclei. In this latter trait,
they are similar to the primitive
prokaryotic cells of bacteria. Red cells normally
make up 40-50% of the total blood volume. They transport oxygen from the
lungs to all of the living tissues of the body and carry away carbon dioxide.
The red cells are produced continuously in our bone marrow from
stem cells at a rate of about 2-3
million cells per second.
Hemoglobin is the gas transporting protein molecule that makes up 95% of a
red cell. Each red cell has about 270,000,000 iron-rich hemoglobin molecules. People who
are anemic generally have a deficiency in red cells, and subsequently feel
fatigued due to a shortage of oxygen. The red color of blood
is primarily due to oxygenated red cells. Human fetal hemoglobin
molecules differ from those produced by adults in the number of amino acid
chains. Fetal hemoglobin has three chains, while adults produce only
two. As a consequence, fetal hemoglobin molecules attract and
transport relatively more oxygen to the cells of the body.

White
Cells

White cells, or leukocytes, exist in
variable numbers and types but make up a very small part of blood's volume--normally
only about 1% in healthy people. Leukocytes are not limited to blood. They occur
elsewhere in the body as well, most notably in the spleen, liver, and lymph
glands. Most are produced in our bone marrow from the same kind
of stem cells that produce red blood cells. Others are produced in the
thymus gland, which is at the base of the neck. Some white
cells (called lymphocytes)
are the first responders for our immune system. They seek out, identify,
and bind to alien protein on bacteria,
viruses, and fungi
so that they can be removed.
Other white cells (called granulocytes
and macrophages)
then arrive to surround and destroy the alien cells. They also
have the function of getting rid of dead or dying blood cells
as well as foreign matter such as dust and asbestos. Red
cells remain viable for only about 4 months before they are removed from the
blood and their components recycled in the spleen. Individual white
cells usually only last 18-36 hours before they also are removed, though some
types live as much as a year. The description of white cells presented
here is a simplification. There are actually many specialized
sub-types of them that participate in different ways in our immune
responses.

Platelets

erythrocyte (left),
thrombocyte
(center), and leukocyte (right)

Platelets , or
thrombocytes, are cell
fragments without nuclei that work with blood clotting chemicals at the site of wounds.
They do this by adhering to the walls of blood vessels, thereby plugging the rupture in
the vascular wall. They also can
release coagulating chemicals which cause clots to form in the blood that
can plug up narrowed blood vessels. Thirteen different blood clotting
factors, in addition to platelets, need to interact for clotting to occur.
They do so in a cascading manner, one factor triggering another.
Hemophiliacs lack the ability to produce either blood factor 8 or 9.

Platelets are not equally effective in
clotting blood throughout the entire day. The body's circadian rhythm
system (its internal biological clock) causes the peak of platelet
activation in the morning. This is one of the main reasons that
strokes and heart attacks are more common in the morning.

Recent research has shown that platelets
also
help fight infections by releasing proteins that kill invading bacteria and
some other microorganisms. In addition, platelets stimulate the immune
system. Individual platelets are about 1/3 the size of red cells. They
have a lifespan of 9-10 days. Like the red and white blood cells, platelets
are produced in bone marrow from stem cells.

Plasma

Plasma is the relatively clear,
yellow tinted water (92+%), sugar, fat, protein and salt
solution which carries the red
cells, white cells, and platelets. Normally, 55% of our blood's volume is made up of
plasma. As the heart pumps blood to cells throughout the body, plasma brings nourishment
to them and removes the waste products of metabolism. Plasma also contains blood clotting factors, sugars, lipids,
vitamins, minerals, hormones, enzymes,
antibodies, and other
proteins. It is likely that plasma
contains some of every protein produced by the body--approximately 500 have been identified in
human plasma so far.

Blood
Components--animated view of the major blood components.This link takes
you to an external website. To return here, you must
click the "back" button on your browser program.
(length = 53 secs)

Agglutination

Sometimes when the blood of two people is mixed
together, it
clumps or forms visible islands in the liquid plasma--the red cells become attached to one
another. This is agglutination .

Unagglutinated blood smear

Agglutinated blood

When
different types of blood are mixed within the body, the reaction can be a
bursting of the red cells as well as agglutination. Different types of blood are
recognized on the molecular level and sometimes rejected by being destroyed and
ultimately filtered out by the kidneys in order to expel them from the body along with
urine. In the case of a transfusion mistake, there can be so much of the wrong type
of blood in the system that it can result in kidney failure and death. This is due
to the fact that when the kidneys try to filter the blood, they essentially become clogged
as they are overwhelmed and cease being effective filters. Additionally,
there is a rapid depletion of blood clotting factors which causes bleeding
from every body orifice. In the United States, about 1 in 12,000 units
of whole blood transfused is given to the wrong person. Depending on
the blood types of the donor and the recipient, this can result in death or
no problems at all.

The
compositional difference between blood types is in the specific kinds of
antigens found on the surface
of the red cells. Antigens are relatively large protein molecules that provide the biological signature
of an individual's blood type.

(not actual shape or
size of antigens)

Within
blood, there are substances called antibodies
which
distinguish particular antigens from others, causing bursting or agglutination
of the red cells when
alien antigens are found. The antibodies bind to the antigens. In
the case of agglutination, the antibodies "glue" together the antigens from different
red cells thereby sticking the red cells together (as shown below on the right).

Antibodies seeking specific antigens

Antibodies agglutinating red cells

(not actual shape or size of antigens and antibodies)

As agglutination proceeds, millions of red
cells are glued together into clumps. This is not the
same thing as clotting. When agglutination occurs, the blood mostly remains
liquid. With clotting, however, it does not.

The
specific types of antigens on our red blood cells determine our blood types. There are
29 known human blood systems, or groups, for which each of us can be typed.
As a result, there are one or more antigens for each of these blood groups.
Since many of these blood systems also are found in apes and monkeys, it is
likely that they evolved prior to the time that we became a separate
species.

History of Blood
Transfusions

Long
before the phenomenon of blood antigen-antibody interaction was discovered,
surgeons experimented with human transfusions in an attempt to save the lives of
patients who were dying from severe blood loss and the resulting shock.
The first attempt may have been an English physician during the mid-17th
century who infused a wounded soldier with sheep blood. Not
surprisingly, the soldier suffered a painful death. The first successful
transfusion of human blood to another human was done by a British doctor in
1818 in order to save the life of a woman who was hemorrhaging following
childbirth. By the mid 19th
century, European and American doctors used transfusions in a last ditch
attempt to save soldiers and other patients with horrendous wounds. They
usually transferred blood directly from a healthy individual to their patient
via a rubber tube with hypodermic needles at each end. This occasionally
resulted in success but more often than not killed the recipient. The
results seemed to be random. Doctors in the 19th century also
experimented with a variety of blood substitutes, including milk, water, and
even oils.

It was the discovery of the ABO
blood types in 1900 that finally led us to understand how to consistently use
transfusions to save lives. Even with this knowledge, however, life
threatening reactions still occur in about 1 out of 80,000 transfusions in
developed nations. The ABO blood group and its central role in
transfusion failures are described in the next
section of this tutorial.

The blood
type
antigen-antibody interaction is one of many similar
recognition-rejection
phenomena in our bodies. Infectious microorganisms, such as viruses,
also carry foreign antigens which stimulate the production of white cell
antibodies (lymphocytes) that attack the antigens by binding to them as a way
of getting rid of the invading parasites. Once stem cells in our bone
marrow produce antibodies to identify a specific alien antigen, we have the
ability to produce them more quickly and in larger numbers. This results
in the development of a long-term active immunity to future invasions of the
same kind of alien antigen. This is the key to successful vaccination
for viruses and some other microorganisms that invade our bodies.

Immune Cells in Action--developing
immunity to a virus via the antigen-antibody interaction.This link takes you to a
QuickTime video. To return here, you must click the "back"
button
on your browser program.
(length = 1 min, 40 secs)

White cell antibodies are also responsible
for recognizing and rejecting alien body tissues, or, more accurately, the
antigens on their cells. This is the main
reason that organ transplants were most often unsuccessful in the past until the creation
of drugs that can suppress the immune system and thereby prevent organ
rejection. The immune system that is responsible is called the
human leukocyte antigen (HLA)system. This is by far the most
polymorphic of all known human
genetic systems--there are more than 100 antigens on tissue cells in humans
resulting in approximately 30,000,000 possible HLA
genotypes. The chance of two
unrelated people having the same HLA genotypes is very slim.
Subsequently, HLA incompatibility between organ donors and recipients are
common.

NOTE: Antibodies are also known as
"agglutinins" and antigens as "agglutinogens". This alternative
terminology is not used here because of the potential confusion of similar
words.

NOTE:
It is now known that the blood of some women who have been pregnant can cause
a life-threatening reaction in people who receive transfusions from them.
This reaction is known as "transfusion-related acute lung injury" (TRALI).
This can occur if the donor's blood contains antibodies produced by her body
during a pregnancy in order to prevent rejection of blood cell antigens in
male fetuses. The likelihood of this occurring apparently is higher
for women who have given birth more than once. TRALI apparently is
mainly a problem if the blood recipient receives plasma rather than whole
blood. Because of the risk, the American Red Cross is shifting to
using 95% male plasma donors. In the recent past, it has been 50%
male.